Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
J Biomol Struct Dyn. 2022 Feb;40(3):1101-1108. doi: 10.1080/07391102.2020.1822209. Epub 2020 Sep 18.
The spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a worldwide outbreak of coronavirus disease 19 (COVID-19), which rapidly evolved as a global concern. The efforts of the scientific community are pointed towards the identification of promptly available therapeutic options. RNA-dependent RNA polymerase (RdRp) is a promising target for developing small molecules to contrast SARS-CoV-2 replication. Modern computational tools can boost identification and repurposing of known drugs targeting RdRp. We here report the results regarding the screening of a database containing more than 8800 molecules, including approved, experimental, nutraceutical, illicit, withdrawn and investigational compounds. The molecules were docked against the cryo-electron microscopy structure of SARS-CoV-2 RdRp, optimized by means of molecular dynamics (MD) simulations. The adopted three-stage docking study underline that compounds formerly developed as kinase inhibitors may interact with RdRp.Communicated by Ramaswamy H. Sarma.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的传播导致了 19 型冠状病毒病（COVID-19）的全球爆发，这迅速成为全球关注的焦点。科学界正在努力寻找及时可用的治疗选择。RNA 依赖性 RNA 聚合酶（RdRp）是开发小分子来对抗 SARS-CoV-2 复制的有前途的靶标。现代计算工具可以促进鉴定和重新利用针对 RdRp 的已知药物。我们在此报告对包含 8800 多种分子的数据库进行筛选的结果，这些分子包括已批准、实验性、营养性、非法、撤回和研究性化合物。这些分子通过对接 Cryo-EM 结构的 SARS-CoV-2 RdRp 进行对接，并通过分子动力学（MD）模拟进行优化。所采用的三阶段对接研究表明，以前作为激酶抑制剂开发的化合物可能与 RdRp 相互作用。
